Bright Futures

The latest Center for Disease Control and Prevention (CDC) report suggests that Autism Spectrum Disorder (ASD) affects almost 2% of children. Most outstanding, the report finds the prevalence continues to increase and the age of diagnosis has not decreased over the last 20 years. Based on these facts, it’s easy to understand why there is a national health observance dedicated to autism. It also parallels my experience with ASD and is what drove me to develop a personalized medicine approach to treating ASD, as well as a research program to find new treatments for ASD.

About 15 years ago, I started specializing in treating children with ASD. This was fueled by parents who came to my clinic wanting answers as to why their children developed this disorder and what could be done about it.

When I started on my journey with ASD, little was known about the causes and effective treatments, and we have only made marginal progress over the last decade. About 10 years ago, myself and a colleague pointed out an upward trend in investigating abnormalities in the body’s physiological as well as the environment. We pointed out the importance of the mitochondria, oxidative stress and the immune system in ASD. Understanding the underlying biology of ASD has the potential to develop new targeted treatments. It is important to understand not every potentially good sounding treatment is effective, so we need carefully performed clinical trials to determine which treatments are indeed effective and which just sound like good ideas.

The first success was the finding that many children with ASD (~75%) have an antibody in their blood which blocks the ability of folate to enter the brain. We discovered this by carefully studying our clinic patients using a research protocol that allowed us to mine clinical data - an approach I have continued to use to discover new subtypes of ASD as well as search for effective treatments. My first study found that a special prescription form of folate, known as leucovorin, could substantially improve language in children with ASD. This was an open-label study from a clinic population which, scientifically, was open to biases. The next step was to prove the results were repeatable under carefully controlled conditions. The second study found leucovorin was indeed helpful for children with ASD - especially those positive for the folate receptor autoantibody in their blood. This study was rated as the second most important research study on ASD in 2018 by Autism Speaks. The exciting thing is that at Barrow Neurological Institute at Phoenix Children’s, we are extending this research to investigate the next advancement in leucovorin through leading three multicenter clinical trials funded by the National Institutes of Health, Autism Speaks and the Department of Defense. In one of these studies, we are also using advanced neuroimaging to better understand the brain pathways that are changed by this novel treatment.

About 10 years ago, we pointed out the mitochondria, the powerhouse of the cell, is important in ASD. As such, we have launched the first controlled clinical trial to understanding whether a treatment directed at improving mitochondrial function can help children with ASD. In addition, in an observational study, we are examining the effect of mitochondrial function in the wider ASD population to better understand the significance of mitochondrial dysfunction.

We are also investigating the effect of transdermal neuromodulation to improve anxiety and sleep in adolescents and young adults with ASD. Because the stimulation is at high frequencies, it is painless and imperceivable. Similar devices have been used for migraine headaches and attention deficit disorder and can be used at home, so demonstrating the effectiveness of this treatment could provide an effective treatment for a symptom that is difficult to treat and improve the lives of many individuals with ASD who are transitioning into adulthood.

Research into effective treatments for ASD is only beginning. These clinical trials are important so we can better understand which treatments are effective, as well as which treatments are most appropriate for which children.  It is likely new medical treatments will enhance rather than replace behavioral and educational therapy, so it is important to start such therapy early in life. It is essential for parents and caretakers to understand that research requires them to participate. It can be challenging for parents to take on the added responsibility of being in a clinical trial, but these studies are essential for moving forward the understanding of the causes and treatment for ASD.

For those interested in our studies, please contact us at AutismResearch@phoenixchildrens.com.